Genetic Variant NM_001252102.2:c.4391C>T (chr1-200976828-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001252102.2(KIF21B):c.4391C>T(p.Thr1464Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000706 in 1,613,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

KIF21B
NM_001252102.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

Publications

3 publications found

Variant links:

Genes affected

KIF21B (HGNC:29442): (kinesin family member 21B) This gene encodes a member of the kinesin superfamily. Kinesins are ATP-dependent microtubule-based motor proteins that are involved in the intracellular transport of membranous organelles. Single nucleotide polymorphisms in this gene are associated with inflammatory bowel disease and multiple sclerosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

KIF21B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27563608).

BS2

High AC in GnomAd4 at 34 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001252102.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF21B	NM_001252102.2	MANE Select	c.4391C>T	p.Thr1464Met	missense	Exon 32 of 35	NP_001239031.1	O75037-4
KIF21B	NM_001252100.2		c.4391C>T	p.Thr1464Met	missense	Exon 32 of 35	NP_001239029.1	O75037-1
KIF21B	NM_017596.4		c.4352C>T	p.Thr1451Met	missense	Exon 31 of 34	NP_060066.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF21B	ENST00000461742.7	TSL:1 MANE Select	c.4391C>T	p.Thr1464Met	missense	Exon 32 of 35	ENSP00000433808.1	O75037-4
KIF21B	ENST00000422435.2	TSL:1	c.4391C>T	p.Thr1464Met	missense	Exon 32 of 35	ENSP00000411831.2	O75037-1
KIF21B	ENST00000332129.6	TSL:1	c.4352C>T	p.Thr1451Met	missense	Exon 31 of 34	ENSP00000328494.2	O75037-2

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000399

AC:

AN:

250706

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000547

AC:

AN:

1461398

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

726948

show subpopulations

African (AFR)

AF:

0.000687

AC:

AN:

33474

American (AMR)

AF:

0.0000672

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000387

AC:

AN:

1111732

Other (OTH)

AF:

0.000149

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000223

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.000700

AC:

AN:

41456

American (AMR)

AF:

0.000196

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.000283

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

Eigen

Benign

0.016

Eigen_PC

Benign

0.020

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

M_CAP

Benign

0.020

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

PhyloP100

4.1

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.4

REVEL

Benign

0.088

Sift

Benign

0.13

Sift4G

Benign

0.23

Polyphen

0.68

Vest4

0.59

MVP

0.41

MPC

1.4

ClinPred

0.093

GERP RS

4.0

Varity_R

0.033

gMVP

0.22

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over